Improvement in the ability to have sex in patients with Peyronie's disease treated with Collagenase Clostridium histolyticum.

Objective: To describe the results of intralesional Collagenase Clostridium histolyticum (CCH) treatment in patients with Peyronie's disease (PD) in real-world setting. PD is characterized by curvature of the erect penis caused by fibrotic tissue in the tunica albuginea. Patients and methods: Patients with stable PD and curvature of 30° to 90° were prospectively enrolled. CCH injections were initially given using a scheme of four cycles of two injections within 48-72 h every 6 weeks. Later using a modified scheme of three injections every 4 weeks, combined with a vacuum erection device (VED) twice daily. All patients were requested to take pictures of the erect penis prior to and following treatment, from above and laterally. Curvature was measured by three independent researchers based on the provided pictures using a goniometer. Furthermore, patients filled in the Peyronie Disease Questionnaire-NL (PDQ-NL) and Patient Reported Outcome Measurement (PROM).The primary outcome was reduction in curvature and the ability to have penetrating sex again. Secondary outcomes include pain scores during injections, changes in PDQ-NL, PROM and complications of CCH treatment. Results: Sixty-three patients were included, mean age was 56.0 years (range 39-70) and mean reduction in curvature 20.6° (SD 10.2, range 5-49); 74.5% of the patients were able to have penetrating sex again following treatment, compared with 41.2% prior to treatment. According to the PROM questions, sexual improvement was seen in 66.7% of patients. The satisfaction rate was 6.8 (SD 1.8). All patients save two recommend treatment. Conclusions: Intralesional treatment with CCH in men with PD leads to a mean curvature improvement of 20.6°. Following treatment, 74.5% of men were able to have sexual intercourse and 54.9% of the couples were satisfied with their sex life. No major complications occurred in the patients treated with CCH. CCH is not available in Europe anymore despite good results.

Incidence of significant prostate cancer after negative MRI and systematic biopsy in the FUTURE trial.

OBJECTIVES: To assess the proportion of clinically significant (cs) prostate cancer (PCa) found during follow-up in patients with negative systematic biopsy (SB) followed by non-suspicious multiparametric magnetic resonance imaging (mpMRI) and persistent clinical suspicion of PCa compared to the general population. PATIENTS AND METHODS: A prospective study in a subgroup of patients from a multicentre randomized controlled trial was conducted between 2014 and 2017, including 665 men with prior negative SB with a persistent elevated prostate-specific antigen and/or suspicious digital rectal examination undergoing mpMRI. All patients with negative SB and Prostate Imaging-Reporting and Data System (PI-RADS) ≤2 on mpMRI entered biochemical follow-up. Follow-up data until December 2021 were collected by reviewing institutional hospital records and the Dutch Pathology Registry (PALGA). The primary outcome was the observed number of csPCa (Gleason ≥3 + 4/International Society of Urological Pathology grade group ≥2) cases during follow-up compared to the expected number in the general population (standardized incidence ratio [SIR]). RESULTS: In total, 431 patients had non-suspicious mpMRI and entered biochemical follow-up. After a median (interquartile range) follow-up of 41 (23-57) months, 38 patients were diagnosed with PCa, of whom 13 (3.0%) had csPCa. The SIR for csPCa was 4.3 (95% confidence interval 2.3-7.4; total excess of eight cases). A higher risk of a positive biopsy for (cs)PCa based on the European Randomized Study of Screening for Prostate Cancer risk calculator and a suspicious repeat MRI (PI-RADS ≥3) were significant predictive factors for csPCa. CONCLUSION: After negative prior biopsy and non-suspicious mpMRI the risk of csPCa is low. However, compared to the general population, the risk of csPCa is increased despite the high negative predictive value of mpMRI. More research focusing on biochemical and image-guided risk-adapted diagnostic surveillance strategies is warranted.

Is There Still a Need for Repeated Systematic Biopsies in Patients with Previous Negative Biopsies in the Era of Magnetic Resonance Imaging-targeted Biopsies of the Prostate?

BACKGROUND: The role of targeted prostate biopsies (TBs) in patients with cancer suspicious lesions on multiparametric magnetic resonance imaging (mpMRI) following negative systematic biopsies (SBs) is undebated. However, whether they should be combined with repeated SBs remains unclear. OBJECTIVE: To evaluate the value of repeated SBs in addition to TBs in patients with a prior negative SB and a persistent suspicion of prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: A prospective study as part of a multicenter randomized controlled trial conducted between 2014 and 2017, including 665 men with a prior negative SB and a persistent suspicion of PCa (suspicious digital rectal examination and/or prostate-specific antigen >4.0ng/ml). INTERVENTION: All patients underwent 3T mpMRI according to Prostate Imaging Reporting and Data System (PI-RADS) v2. Patients with PI-RADS ≥3 were randomized 1:1:1 for three TB techniques: MRI-TRUS fusion TB (FUS-TB), cognitive registration fusion TB (COG-TB), or in-bore MRI TB. FUS-TB and COG-TB were combined with repeated SBs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinically significant prostate cancer (csPCa) was defined as Gleason ≥3+4. Differences in detection rates of csPCa, clinically insignificant PCa (cisPCa), and overall PCa between TBs (FUS-TB and COG-TB) and repeated SBs were compared using McNemar's test. RESULTS AND LIMITATIONS: In the 152 patients who underwent both TB and SB, PCa was detected by TB in 47% and by SB in 32% (p<0.001, 95% confidence interval [CI]: 6.0-22%). TB detected significantly more csPCa than SB (32% vs 16%; p<0.001, 95% CI: 11-25%). Clinically significant PCa was missed by TB in 1.3% (2/152). Combining SB and TB resulted in detection rate differences of 6.0% for PCa, 5.0% for cisPCa, and 1.0% for csPCa compared with TB alone. CONCLUSIONS: In case of a persistent suspicion of PCa following a negative SB, TB detected significantly more csPCa cases than SB. The additional value of SB was limited, and only 1.3% of csPCa would have been missed when SB had been omitted. PATIENT SUMMARY: We evaluated the role of systematic biopsies and magnetic resonance imaging (MRI)-targeted biopsies for the diagnosis of prostate cancer in patients with prior negative systematic biopsies. MRI-targeted biopsies perform better in detecting prostate cancer in these patients. The value of repeated systematic biopsies is limited.

Complications and Adverse Events of Three Magnetic Resonance Imaging-based Target Biopsy Techniques in the Diagnosis of Prostate Cancer Among Men with Prior Negative Biopsies: Results from the FUTURE Trial, a Multicentre Randomised Controlled Trial.

BACKGROUND: Three techniques of magnetic resonance imaging (MRI)-based targeted biopsy (TB) of the prostate exist. There is no superiority regarding diagnostic efficacy of prostate cancer (PCa) detection. OBJECTIVE: To compare adverse events (AEs) among three TB techniques and to evaluate the effect on urinary and erectile function. DESIGN, SETTING, AND PARTICIPANTS: Post hoc analysis of a multicentre randomised controlled trial among men with negative systematic biopsy (SB) and suspicion of PCa. INTERVENTION: In 234 patients, 3-T multiparametric MRI demonstrated PIRADS≥ 3 lesions, and patients were randomised 1:1:1 for TB: transrectal in-bore MRI TB (MRI-TB), transperineal MRI-transrectal ultrasound (TRUS) fusion TB (FUS-TB), and transrectal cognitive TRUS TB (COG-TB). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: AEs (Clavien-Dindo) were compared using Pearson chi-square test. Univariate logistic regression tests were performed for the number of cores, biopsy approach, and usage of anticoagulants. The participants filled in baseline and 30-d postbiopsy International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) questionnaires. The delta between measurements was compared using one-way analysis of variance. RESULTS AND LIMITATIONS: There were significant differences in minor AEs: 53% in MRI-TB, 71% in FUS-TB, and 85% in COG-TB (p < 0.001). The number of cores was associated with AEs (odds ratio [OR] 1.11 per extra biopsy [95% confidence interval {CI} 1.06-1.17, p < 0.001]). Anticoagulants were not associated with bleeding complications (OR 1.24 [95% CI 0.66-2.35, p = 0.5]). Transrectal approach (MRI-TB + COG-TB) increased the risk of any AE (OR 2.54 [95% CI 1.16-5.77, p < 0.05]) and nonsignificantly increased the risk of urinary tract infections (OR 3.69 [95% CI 0.46-168.4, p = 0.3]). Biopsy did not impact urinary (ΔIPSS 0.3, p = 0.1) and erectile function (ΔIIEF-5 -0.4, p = 0.5). The main limitation was that additional SB was performed in FUS-TB and COG-TB, and was omitted in MRI-TB, making comparison difficult. CONCLUSIONS: There was a significant difference in minor AEs among groups. An increase in the number of cores increased the overall risk of AEs. A low AE occurrence in MRI-TB was likely caused by the omission of SB. Prostate biopsy did not impact self-reported urinary and erectile functions. PATIENT SUMMARY: In this study, we compared the complication rates of three techniques of magnetic resonance imaging (MRI)-based targeted biopsy of the prostate. We found a significant difference in the occurrence of minor complication rates among three groups in favour of transrectal in-bore MRI targeted biopsy, likely caused by the omission of additional systematic biopsy in this group.

The FUTURE Trial: A Multicenter Randomised Controlled Trial on Target Biopsy Techniques Based on Magnetic Resonance Imaging in the Diagnosis of Prostate Cancer in Patients with Prior Negative Biopsies.

BACKGROUND: Guidelines advise multiparametric magnetic resonance imaging (mpMRI) before repeat biopsy in patients with negative systematic biopsy (SB) and a suspicion of prostate cancer (PCa), enabling MRI targeted biopsy (TB). No consensus exists regarding which of the three available techniques of TB should be preferred. OBJECTIVE: To compare detection rates of overall PCa and clinically significant PCa (csPCa) for the three MRI-based TB techniques. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomised controlled trial, including 665 men with prior negative SB and a persistent suspicion of PCa, conducted between 2014 and 2017 in two nonacademic teaching hospitals and an academic hospital. INTERVENTION: All patients underwent 3-T mpMRI evaluated with Prostate Imaging Reporting and Data System (PIRADS) version 2. If imaging demonstrated PIRADS ≥3 lesions, patients were randomised 1:1:1 for one TB technique: MRI-transrectal ultrasound (TRUS) fusion TB (FUS-TB), cognitive registration TRUS TB (COG-TB), or in-bore MRI TB (MRI-TB). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary (overall PCa detection) and secondary (csPCa detection [Gleason score ≥3+4]) outcomes were compared using Pearson chi-square test. RESULTS AND LIMITATIONS: On mpMRI, 234/665 (35%) patients had PIRADS ≥3 lesions and underwent TB. There were no significant differences in the detection rates of overall PCa (FUS-TB 49%, COG-TB 44%, MRI-TB 55%, p=0.4). PCa detection rate differences were -5% between FUS-TB and MRI-TB (p=0.5, 95% confidence interval [CI] -21% to 11%), 6% between FUS-TB and COG-TB (p=0.5, 95% CI -10% to 21%), and -11% between COG-TB and MRI-TB (p=0.17, 95% CI -26% to 5%). There were no significant differences in the detection rates of csPCa (FUS-TB 34%, COG-TB 33%, MRI-TB 33%, p>0.9). Differences in csPCa detection rates were 2% between FUS-TB and MRI-TB (p=0.8, 95% CI -13% to 16%), 1% between FUS-TB and COG-TB (p>0.9, 95% CI -14% to 16%), and 1% between COG-TB and MRI-TB (p>0.9, 95% CI -14% to 16%). The main study limitation was a low rate of PIRADS ≥3 lesions on mpMRI, causing underpowering for primary outcome. CONCLUSIONS: We found no significant differences in the detection rates of (cs)PCa among the three MRI-based TB techniques. PATIENT SUMMARY: In this study, we compared the detection rates of (aggressive) prostate cancer among men with prior negative biopsies and a persistent suspicion of cancer using three different techniques of targeted biopsy based on magnetic resonance imaging. We found no significant differences in the detection rates of (aggressive) prostate cancer among the three techniques.

Comparing Three Different Techniques for Magnetic Resonance Imaging-targeted Prostate Biopsies: A Systematic Review of In-bore versus Magnetic Resonance Imaging-transrectal Ultrasound fusion versus Cognitive Registration. Is There a Preferred Technique?

CONTEXT: The introduction of magnetic resonance imaging-guided biopsies (MRI-GB) has changed the paradigm concerning prostate biopsies. Three techniques of MRI-GB are available: (1) in-bore MRI target biopsy (MRI-TB), (2) MRI-transrectal ultrasound fusion (FUS-TB), and (3) cognitive registration (COG-TB). OBJECTIVE: To evaluate whether MRI-GB has increased detection rates of (clinically significant) prostate cancer (PCa) compared with transrectal ultrasound-guided biopsy (TRUS-GB) in patients at risk for PCa, and which technique of MRI-GB has the highest detection rate of (clinically significant) PCa. EVIDENCE ACQUISITION: We performed a literature search in PubMed, Embase, and CENTRAL databases. Studies were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 checklist and START recommendations. The initial search identified 2562 studies and 43 were included in the meta-analysis. EVIDENCE SYNTHESIS: Among the included studies 11 used MRI-TB, 17 used FUS-TB, 11 used COG-TB, and four used a combination of techniques. In 34 studies concurrent TRUS-GB was performed. There was no significant difference between MRI-GB (all techniques combined) and TRUS-GB for overall PCa detection (relative risk [RR] 0.97 [0.90-1.07]). MRI-GB had higher detection rates of clinically significant PCa (csPCa) compared with TRUS-GB (RR 1.16 [1.02-1.32]), and a lower yield of insignificant PCa (RR 0.47 [0.35-0.63]). There was a significant advantage (p = 0.02) of MRI-TB compared with COG-TB for overall PCa detection. For overall PCa detection there was no significant advantage of MRI-TB compared with FUS-TB (p=0.13), and neither for FUS-TB compared with COG-TB (p=0.11). For csPCa detection there was no significant advantage of any one technique of MRI-GB. The impact of lesion characteristics such as size and localisation could not be assessed. CONCLUSIONS: MRI-GB had similar overall PCa detection rates compared with TRUS-GB, increased rates of csPCa, and decreased rates of insignificant PCa. MRI-TB has a superior overall PCa detection compared with COG-TB. FUS-TB and MRI-TB appear to have similar detection rates. Head-to-head comparisons of MRI-GB techniques are limited and are needed to confirm our findings. PATIENT SUMMARY: Our review shows that magnetic resonance imaging-guided biopsy detects more clinically significant prostate cancer (PCa) and less insignificant PCa compared with systematic biopsy in men at risk for PCa.

An Ex Vivo Phantom Validation Study of an MRI-Transrectal Ultrasound Fusion Device for Targeted Prostate Biopsy.

OBJECTIVES: To evaluate the ex vivo accuracy of an MRI-TRUS fusion device for guiding targeted prostate biopsies, to identify the origin of errors, and to evaluate the likelihood that lesions can be accurately targeted. MATERIALS AND METHODS: Three prostate phantoms were used to perform 27 biopsies using transperineal MRI-TRUS fusion. All phantoms underwent 3-T MRI. The prostate contour and nine lesions were delineated onto the MRI. A 3D-US dataset was generated and fused with the MRI. Per lesion, one needle was virtually planned. The postbiopsy needle location was virtually registered. The needle trajectory was marked using an MRI-safe guidewire. Postinterventional MRI was performed. The coordinates of the lesion on preinterventional MRI, the virtually planned needle, the virtually registered needle, and the marked needle trajectory on postinterventional MRI were documented and used to calculate the planning error (PE), targeting error (TE), and overall error (OE). Using the OE in the transversal plane, an upper one-sided tolerance interval was calculated to assess the likelihood that a biopsy needle was on target. RESULTS: In the transversal plane, the mean PE, TE, and OE were 1.18, 0.39, and 2.33 mm, respectively. Using a single biopsy core, the likelihood that lesions with a diameter of 2 mm can be accurately targeted is 26%; lesions of 3 mm 61%; lesions of 4 mm 86%; lesions of 5 mm 96%; and lesions of 6 mm 99%. The likelihood of accurate sampling increases if more biopsy cores are used. CONCLUSION: MRI-TRUS fusion allows for accurate sampling of MRI-identified lesions with an OE of 2.33 mm. Lesions with a diameter of 3 mm or more can be accurately targeted. These results should be considered the lower limit of in vivo accuracy.

The Effects of Instrumentation on Urine Cytology and CK-20 Analysis for the Detection of Bladder Cancer.

OBJECTIVE: To evaluate the effects of cystoscopy on urine cytology and additional cytokeratin-20 (CK-20) staining in patients presenting with gross hematuria. PATIENTS AND METHODS: For 83 patients presenting with gross hematuria, spontaneous and instrumented paired urine samples were analyzed. Three patients were excluded. Spontaneous samples were collected within 1 hour before cystoscopy, and the instrumented samples were tapped through the cystoscope. Subsequently, patients underwent cystoscopic evaluation and imaging of the urinary tract. If tumor suspicious lesions were found on cystoscopy or imaging, subjects underwent transurethral resection or ureterorenoscopy. Two blinded uropathological reviewers (DB, KK) evaluated 160 urine samples. Reference standards were results of cystoscopy, imaging, or histopathology. RESULTS: Thirty-seven patients (46.3%) underwent transurethral resection or ureterorenoscopy procedures. In 30 patients (37.5%) tumor presence was confirmed by histopathology. The specificity of urine analysis was significantly higher for spontaneous samples than instrumented samples for both cytology alone (94% vs 72%, P = .01) and for cytology combined with CK-20 analysis (98% vs 84%, P = .02). The difference in sensitivity between spontaneous and instrumented samples was not significant for both cytology alone (40% vs 53%) and combined with CK-20 analysis (67% vs 67%). The addition of CK-20 analysis to cytology significantly increases test sensitivity in spontaneous urine cytology (67% vs 40%, P = .03). CONCLUSION: Instrumentation significantly decreases specificity of urine cytology. This may lead to unnecessary diagnostic procedures. Additional CK-20 staining in spontaneous urine cytology significantly increases sensitivity but did not improve the already high specificity. We suggest performing urine cytology and CK-20 analysis on spontaneously voided urine.